Cesium carbonate → HCID 118079449, compound

HRID 1485743Notes

Reaction equation

HRID 1485743 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17](Br)[CH:18]=2)[N:13]([C:21]([CH:23]2[CH2:25][CH2:24]2)=[O:22])[C@@H:12]([CH3:26])[CH2:11]1.[CH:27]1([N:30]2[CH:34]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:32]=[N:31]2)[CH2:29][CH2:28]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:33]3[CH:32]=[N:31][N:30]([CH:27]4[CH2:29][CH2:28]4)[CH:34]=3)[CH:18]=2)[N:13]([C:21]([CH:23]2[CH2:25][CH2:24]2)=[O:22])[C@@H:12]([CH3:26])[CH2:11]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 593271331-Cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118079498HCID 118079498, compound

Product 1

HCID 118079449HCID 118079449, compoundYield 69.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-(4-(benzo[d]oxazol-2-yl)-6-bromo-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)(cyclopropyl)methanone (0.019 g, 0.046 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.012 g, 0.051 mmol), tris(dibenzylideneacetone)dipalladium (2.1 mg, 2.3 μmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (XPhos) (2.2 mg, 4.6 μmol) and cesium carbonate (0.045 g, 0.138 mmol) in dioxane (1.0 mL) and water (0.20 mL) was heated in the microwave at 100° C. for 1.5 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100% ethyl acetate-hexane) to afford (S)-(4-(benzo[d]oxazol-2-yl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxaline-1(2H)-yl)(cyclopropyl)methanone (0.014 g, 69%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.65-1.05 (m, 11 H), 1.85-2.02 (m, 1 H), 3.58-3.80 (m, 1H), 3.90-4.16 (m, 2 H), 5.02-5.18 (m, 1 H), 7.01-7.26 (m, 2 H), 7.31 (dd, J=8.21, 1.76 Hz, 1 H), 7.35-7.58 (m, 3 H), 7.79 (s, 1 H), 8.18 (s, 1 H), 8.36 (d, J=2.05 Hz, 1 H). MS (ESI, pos. ion) m/z 440 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through Celite
  2. concentrationconcentrated
  3. customto afford an orange oil
  4. customThis material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-8b4011621f2f45a6b522a91b4c83b890
Source dataset
uspto-grants-2016_08
Patent number
US09422281B2

Reaction notes

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